Researchers have scanned the brains of 115 participants and found that inflammation can lead to a loss of pleasure—called anhedonia—in women but not in men.

Depression, the "leading cause of disability worldwide," is far more prevalent in women than it is in men. Worldwide, over 300 million people live with depression. Among young people aged between 14 and 25, females are more than twice as likely to have depression as males. Although these differences become less pronounced in later adulthood, global estimates still show a 1.7-fold increase in the prevalence of depression among women, compared with men.

Anhedonia is one of the hallmarks of major depressive disorder. Anhedonia describes the inability to derive joy or pleasure from activities that used to feel enjoyable. On a neurological level, anhedonia presents itself as reduced activity in the brain's reward processing area, called the ventral striatum.

New research sheds light on how the sex differences in depression manifest themselves in the brain. Specifically, scientists show how inflammation affects the brain's response to rewards differently in men and women. Naomi Eisenberger, PhD, a professor at the University of California, Los Angeles, is the senior author of the paper, which appears in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

Anhedonia as a response to inflammation

Eisenberger and colleagues administered either a low dose of an endotoxin—to induce inflammation—or a placebo to depression-free men and women. In total, the study included 115 participants, 69 of whom were female. The researchers randomly assigned the participants to either the control/placebo group or the low-dose endotoxin group.

Two hours after the intervention, which is the peak of the inflammatory reaction to the toxin, the participants were asked to complete a task in which they had to anticipate a monetary reward. The participants did the task while inside a functional magnetic resonance imaging (MRI) scanner.

The results revealed that the endotoxin reduced the activity of the reward-processing ventral striatum. However, the researchers noticed that this effect differed according to sex.

"Specifically," report Eisenberger and colleagues, "in female participants, endotoxin (vs placebo) led to decreased [ventral striatum] activity in anticipation of reward, but this effect was not present in male participants."

Also, these decreases in the activity of the ventral striatum "were related to increases in inflammation for female but not male participants."

"This suggests that women with chronic inflammatory disorders may be particularly vulnerable to developing depression through decreases in sensitivity to reward," explains first author Mona Moieni, PhD. "Clinicians who treat female patients with inflammatory disorders may want to pay close attention to these patients for possible onset of depressive symptoms," adds Moieni.

"Our study is the first to show that there are sex differences in neural sensitivity to reward in response to inflammation, which has important implications," comments Eisenberger.

"[The findings] may suggest one reason women experience depression at a far greater rate than men, particularly for the kinds of depression that may be inflammatory in nature."

—Naomi Eisenberger, PhD

Dr. Cameron Carter, editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, also comments on the significance of the study. He says that it "highlights the important gender differences that exist in the human brain and suggests a mechanism that might help explain the greater prevalence of depression in women, compared to men."